The myelosuppressed patient with cancer may develop pneumonias which are difficult to diagnose. Thus, aggressive diagnostic procedures are warranted. This study utilized a step-wise, orderly method for diagnosing unexplained pulmonary infiltrates utilizing transtracheal aspiration, transtracheal bronchial brushing, fibroptic bronchoscopy or percutaneous lung biopsies when other methods have failed. Sixty-eight patients with diffuse or nodular infiltrates have undergone such invasive procedures. Sixteen patients were not clinically infected; 10 proved to have pulmonary metastases; 5 proved to have interstitial fibrosis; and 1 proved to have a collapsed lobe. Fifty-two patients were clinically presumed infected. Thirty were proven to have pulmonary infection and 24 of the 30 were etiologically documented by these procedures. Twenty-two of the 52 patients had no etiology established by any method, although 18 of the 22 patients were receiving broad-spectrum antibiotics at the time of the procedure. The diagnosis included a variety of micro-organism: bacterial, protozoal, and fungal. Significant but non-fatal complications occurred and were acceptable risk for the patient population. There was no mortality associated with the procedures, and despite pancytopenia, bleeding was a problem in only 3 patients. This step-wise aggressive diagnostic procedure has proven to be clinically efficacious in 80% of the patients with ultimately documented pneumonias.